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A transcriptional repressor co-regulatory network governing androgen response in prostate cancers
Chng K.R.4; Chang C.W.4; Tan S.K.4; Yang C.4; Hong S.Z.4; Sng N.Y.W.4; Cheung E.4
2012-06-13
Source PublicationEMBO Journal
ISSN02614189 14602075
Volume31Issue:12Pages:2810-2823
Abstract

Transcriptional corepressors are frequently aberrantly over-expressed in prostate cancers. However, their crosstalk with the Androgen receptor (AR), a key player in prostate cancer development, is unclear. Using ChIP-Seq, we generated extensive global binding maps of AR, ERG, and commonly over-expressed transcriptional corepressors including HDAC1, HDAC2, HDAC3, and EZH2 in prostate cancer cells. Surprisingly, our results revealed that ERG, HDACs, and EZH2 are directly involved in androgen-regulated transcription and wired into an AR centric transcriptional network via a spectrum of distal enhancers and/or proximal promoters. Moreover, we showed that similar to ERG, these corepressors function to mediate repression of AR-induced transcription including cytoskeletal genes that promote epithelial differentiation and inhibit metastasis. Specifically, we demonstrated that the direct suppression of Vinculin expression by ERG, EZH2, and HDACs leads to enhanced invasiveness of prostate cancer cells. Taken together, our results highlight a novel mechanism by which, ERG working together with oncogenic corepressors including HDACs and the polycomb protein, EZH2, could impede epithelial differentiation and contribute to prostate cancer progression, through directly modulating the transcriptional output of AR. © 2012 European Molecular Biology Organization.

KeywordAndrogen Receptor Ezh2 Hdac Prostate Cancer Tmprss2:Erg
DOI10.1038/emboj.2012.112
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000305299200015
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Cited Times [WOS]:95   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Nanyang Technological University
2.National University of Singapore
3.Yong Loo Lin School of Medicine
4.A-Star, Genome Institute of Singapore
Recommended Citation
GB/T 7714
Chng K.R.,Chang C.W.,Tan S.K.,et al. A transcriptional repressor co-regulatory network governing androgen response in prostate cancers[J]. EMBO Journal,2012,31(12):2810-2823.
APA Chng K.R..,Chang C.W..,Tan S.K..,Yang C..,Hong S.Z..,...&Cheung E..(2012).A transcriptional repressor co-regulatory network governing androgen response in prostate cancers.EMBO Journal,31(12),2810-2823.
MLA Chng K.R.,et al."A transcriptional repressor co-regulatory network governing androgen response in prostate cancers".EMBO Journal 31.12(2012):2810-2823.
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